Candidate: Dr. Ariadne Letra is a Postdoctoral Associate fellow at the University of Pittsburgh School of Dental Medicine. Her main research interests are genetics of oral-facial clefts. Her short-term goals are to improve knowledge of the multifactorial etiology of this condition and perform genetic studies of complex oral traits. The candidate also wishes to gain expertise in advanced statistical genetics and molecular biology to develop biological functional assays. Her long-term goal is to become an independent scientist and occupy a tenure track position at an Institution. This proposal reflects the plan of the candidate to engage in mentored-research meanwhile building a strong foundation for career development. The research plan is innovative as it proposes to study the family of matrix metalloproteinase genes which have been shown to have important roles during craniofacial development and implicated in cleft lip/palate. The candidate has important preliminary data that further support such evidence. Mentors: Dr. Alexandre Vieira will be the primary mentor for this proposal. He is the principal investigator on a grant for the expansion of the cleft phenotype in genetic studies of oral clefts and has a lot of expertise in studies with craniofacial and dental genetic disorders, with an impressive record of important publications. Dr. Mary Marazita will be the co-mentor for this proposal. She is an expert in statistical genetics and an acknowledged and well-funded researcher. She has extensive experience with mentoring trainees. Environment: the University of Pittsburgh has a long-standing track record of providing postdoctoral fellows with exceptional research and career development training, and offers great support for a successful transition into independent researcher. The School of Dental Medicine is fully committed to providing the candidate with an assistant professor position following the mentored-phase of the award. Research plan: specific aims for the K99 phase include replicate previous findings and investigate polymorphisms in all matrix metalloproteinase genes in association with clefting meanwhile improving skills in research design and statistics. For the ROD phase, the candidate wishes to perform functional assays to test the biological effects of genetic variants. Career Development Plan: the candidate plans to use the research plan to track her own progress as a scientist. Commitment of the mentor team will provide the candidate with frequent evaluations regarding scientific improvement and progress in career training.